Over the past several years, new drugs have emerged to expand our treatment armamentarium for type 2 diabetes, and these products have enhanced our understanding of the pathophysiology of type 2 diabetes. Newer therapies include the incretin class. The development of two products in the this class, glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, has demonstrated safe, effective, and beneficial effects that include lower fasting glucose and postprandial glucose, reduction of A1C, and lower risk for hypoglycemia. How DPP-4 Inhibitors Work DPP-4 is an enzyme that degrades endogenous GLP-1. While GLP-1 receptor agonists increase GLP-1 amounts and activity, DPP-4 inhibitors raise endogenous GLP-1 by inhibiting GLP-1 degradation. Levels of DPP-4 are increased by approximately six-fold. This results in increased insulin secretion, as well as a reduction of glucagon stimulation, which then results in improved fasting and postprandial glucose and improvements in A1C. There are currently just a couple of DPP-4 inhibitors available in the United States, but other agents are currently under FDA review. In clinical research, DPP-4 inhibitors have been well tolerated. An important consideration for patients who use these medications is that they are weight neutral and have been associated with a low risk of hypoglycemia. DPP-4 inhibitors are available for once-daily oral administration. This may improve adherence to drug regimens. They are also available in fixed-dosed combination with metformin, which may also be cost-effective and further improve patient adherence. The long-term safety of DPP-4 inhibitors is continuing to accumulate in medical research. Ongoing trials are addressing efficacy of this drug class as well as its role in cardiovascular disease safety. Clinicians should review...